OBJECTIVE Anti-mesangial cell autoantibodies (anti-MC) have been reported in patients with IgA nephropathy and Henoch-Schoenlein purpura. The aim of the current study was to identify anti-MC autoantibodies in sera from patients with lupus nephritis (LN). METHODS 96 serum samples were collected from 96 patients with renal biopsy proven LN. Anti-MC autoantibodies were examined by cellular ELISA and Western blot analysis. In vitro cultured human mesangial cells were used as cell substrate in ELISA and the their soluble proteins in non-reducing conditions were used as antigens in Western-blot analysis. RESULTS 37.5% and 97.9% of the serum samples from patients with LN had anti-MC autoantibodies in cellular ELISA and Western blot analysis respectively, and 12 protein bands could be blotted by the LN sera in Western blot analysis. The percentage of anti-63 000 autoantibody positive samples was significant higher in female patients than that in the male (59.8% vs 21.4%, P < 0.01). The prevalence of anti-74 000, 46 000, and 36 000 autoantibodies were significantly higher in patients with hematuria than that in patients without hematuria (36.8% vs 5.0%, P < 0.01; 34.2% vs 10.0%, P < 0.05; 31.6% vs 5.0%, P < 0.05; respectively). The prevalence of anti-63 000 autoantibodies was also significantly higher in patients with ANA than that in patients without (67.6% vs 16.7%, P < 0.001). The prevalence of anti-18 000 autoantibodies was significantly higher in patients with anti-dsDNA antibodies than that in patients without (61.5% vs 34.4%, P < 0.05). CONCLUSIONS There are heterogeneous anti-MC autoantibodies in sera from patients with LN. Anti-MC autoantibodies may have a pathogenic role in lupus nephritis and some anti-MC autoantibodies may be associated with different clinical manifestations.